GSK-3β mediates cardiac senescence through inhibition of ULK1 directed autophagy

Abstract

Cardiac senescence is the progressive decline in cardiac performance resulting from decline in age related structural and metabolic processes. Aging cardiac myocytes exhibit alterations in fatty acid and glucose oxidation metabolism, activation of innate immune signaling, enhanced fibrosis, mitochondrial dysfunction, endoplasmic reticulum stress, DNA damage, senescence-associated secreting phenotype and impaired autophagy. GSK-3β is an upstream regulator of autophagy through its interaction with ULK1 which regulates the initiation step of autophagy and formation of the autophagosme. Herein, we highlight a novel putative molecular mechanism that functionally links cardiac senescence, hypertrophy and autophagy regulation. Ser9 phosphorylation of GSK-3β is critical for promoting cardiac senescence via reduction in ULK1 phosphorylation at Ser913 and inhibition of autophagy.

Keywords

GSK-3β / senescence / aging / autophagy / ULK1

References

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